20 min listen
A hydrogel-based model of aortic stiffness reveals that microtubules are novel regulators of smooth muscle cell hypertrophy
A hydrogel-based model of aortic stiffness reveals that microtubules are novel regulators of smooth muscle cell hypertrophy
ratings:
Length:
20 minutes
Released:
Nov 25, 2022
Format:
Podcast episode
Description
Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2022.11.23.517637v1?rss=1
Authors: Johnson, R. T., Ahmed, S., Wostear, F., Morris, C. J., Warren, D. T.
Abstract:
Background and Purpose: Decreased aortic compliance is a precursor to numerous cardiovascular diseases. Compliance is regulated by the stiffness of the aortic wall and the vascular smooth muscle cells (VSMCs) within it. During ageing, the extracellular matrix of the aortic wall stiffens, reducing compliance and leading to conditions such as hypertension. In response, VSMCs generate enhanced contractile forces and undergo hypertrophy, promoting VSMC stiffening and further reducing compliance. Due to a lack of suitable in vitro models, the mechanisms driving VSMC hypertrophy in response to matrix stiffness remain poorly defined. Experimental Approach: Human VSMCs were seeded onto polyacrylamide hydrogels whose stiffness mimicked either healthy or aged/diseased aortae. VSMC response to contractile agonist stimulation was measured through changes in cell area and volume. VSMCs were pre-treated with pharmacological agents prior to agonist stimulation to identify regulators of VSMC contractility and hypertrophy. Key Results: VSMCs undergo a differential response to contractile agonist stimulation based on matrix stiffness. On pliable hydrogels, VSMCs contract, decreasing in cell area whereas on rigid hydrogels, VSMCs undergo a hypertrophic response, increasing in area and volume. Microtubule stabilisation prevented hypertrophy whilst leaving VSMC contraction on pliable hydrogels unimpeded. Conversely, microtubule destabilisation inhibited contraction and induced hypertrophy within VSMCs on pliable hydrogels. Conclusions and Implications: In response to enhanced matrix rigidity, VSMC undergo a hypertrophic response as result of decreased microtubule stability. Using standard biological techniques and equipment, we present a screening assay capable of identifying novel regulators of matrix rigidity induced VSMC hypertrophy. This assay can identify both beneficial and deleterious effects of pharmacological agents to cardiovascular health.
Copy rights belong to original authors. Visit the link for more info
Podcast created by Paper Player, LLC
http://biorxiv.org/cgi/content/short/2022.11.23.517637v1?rss=1
Authors: Johnson, R. T., Ahmed, S., Wostear, F., Morris, C. J., Warren, D. T.
Abstract:
Background and Purpose: Decreased aortic compliance is a precursor to numerous cardiovascular diseases. Compliance is regulated by the stiffness of the aortic wall and the vascular smooth muscle cells (VSMCs) within it. During ageing, the extracellular matrix of the aortic wall stiffens, reducing compliance and leading to conditions such as hypertension. In response, VSMCs generate enhanced contractile forces and undergo hypertrophy, promoting VSMC stiffening and further reducing compliance. Due to a lack of suitable in vitro models, the mechanisms driving VSMC hypertrophy in response to matrix stiffness remain poorly defined. Experimental Approach: Human VSMCs were seeded onto polyacrylamide hydrogels whose stiffness mimicked either healthy or aged/diseased aortae. VSMC response to contractile agonist stimulation was measured through changes in cell area and volume. VSMCs were pre-treated with pharmacological agents prior to agonist stimulation to identify regulators of VSMC contractility and hypertrophy. Key Results: VSMCs undergo a differential response to contractile agonist stimulation based on matrix stiffness. On pliable hydrogels, VSMCs contract, decreasing in cell area whereas on rigid hydrogels, VSMCs undergo a hypertrophic response, increasing in area and volume. Microtubule stabilisation prevented hypertrophy whilst leaving VSMC contraction on pliable hydrogels unimpeded. Conversely, microtubule destabilisation inhibited contraction and induced hypertrophy within VSMCs on pliable hydrogels. Conclusions and Implications: In response to enhanced matrix rigidity, VSMC undergo a hypertrophic response as result of decreased microtubule stability. Using standard biological techniques and equipment, we present a screening assay capable of identifying novel regulators of matrix rigidity induced VSMC hypertrophy. This assay can identify both beneficial and deleterious effects of pharmacological agents to cardiovascular health.
Copy rights belong to original authors. Visit the link for more info
Podcast created by Paper Player, LLC
Released:
Nov 25, 2022
Format:
Podcast episode
Titles in the series (100)
Alterations in platelet proteome signature and impaired platelet integrin αIIbβ3 activation in patients with COVID-19 by PaperPlayer biorxiv cell biology